Cancer Causes & Control

, Volume 8, Issue 3, pp 346–355

Aromatic amines and cancer

  • Paolo Vineis
  • Roberta Pirastu


Epidemiological evidence on the relation between aromatic amines and cancer risk is reviewed. In particular, cancer risk in humans resulting from exposure to aromatic amines from occupational sources and tobacco smoking is assessed with reference to ecologic, cohort, and case-control studies. Seven arylamines have been classified by the International Agency for Research on Cancer: benzidine-based dyes and MOCA(4,4'-methylenebis 2-choloroaniline) were considered 'probably' carcinogenic, Group 2A, because of a high level of evidence in experimental animals; two occupational chemicals (2-naphthylamine and benzidine), one drug (Chlornaphazine), and two manufacturing processes (manufacture of auramine and magenta) were included in Group 1 on the basis of 'sufficient' evidence of carcinogenicity in humans. Occupational exposures to aromatic amines explain up to 25 percent of bladder cancers in some areas of Western countries; these estimates might be higher in limited areas of developing countries. Aromatic amines contaminate the ambient air as a component of environmental tobacco smoke. There is increasing evidence that the excess of bladder cancer in smokers is attributable to aromatic amines rather than to other contaminants of tobacco smoke such as polycyclic aromatic hydrocarbons (PAH). A modulating role in the risk of bladder cancer associated with exposure to aromatic amines is played by metabolic polymorphisms, such as the N-acetyltransferase genotype, raising important social and ethical issues. The consistent observation of a difference between men and women in bladder cancer risk, after allowing for known risk factors, suggests consideration of gender-related biological determinants for future investigation.

Arylamines bladder cancer occupational exposure tobacco 


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  1. 1.
    Jeyaratnam J. Transfer of hazardous industries. In: Pearce N, Matos E, Boffetta P, Kogevinas M, eds. Occupational Cancer in Developing Countries. Oxford, UK: Oxford University Press, 1994; C Sci. Pub.No. 129: 23–9.Google Scholar
  2. 2.
    Maclure M, Katz RB, Bryant MS, Skipper PL, Tannenbaum SR. Elevated blood levels of carcinogens in passive smokers. Am J Public Health 1989; 79: 1381–4.Google Scholar
  3. 3.
    International Agency for Research on Cancer. Some Aromatic Amines, Hydrazine and Related Substances, N-nitrosocompounds and Miscellaneous Alkykating Agents Lyon, France: IARC, 1974; IARC Monogr Eval Risks Humans, Vol. 4.Google Scholar
  4. 4.
    US Government. Occupational Safety and Health Standards. Washington DC: US Federal Register 38, 1973; No. 85, 10929.Google Scholar
  5. 5.
    International Labour Office. Cancer of the Bladder among Workers in Aniline Factories. Geneva, Switzerland: ILO, 1921; Studies and Reports, Series F, No 1.Google Scholar
  6. 6.
    Budnick LD, Sokal DC, Falk H, Logue JN, Fox JM. Cancer and birth defects near the Drake Superfund site, Pennsylvania. Arch Environ Health 1984; 39: 409–13.Google Scholar
  7. 7.
    Dolin PJ. A descriptive study of occupation and bladder cancer in England & Wales. Br J Cancer 1992; 65: 476–8.Google Scholar
  8. 8.
    Dolin PJ, Cook-Mozzafari P. Occupation and bladder cancer: a death certificate study. Br J Cancer 1992; 66: 568–78.Google Scholar
  9. 9.
    Viel JF, Challier B. Bladder cancer among French farmers: does exposure to pesticides in vineyards play a part? Occup Environ Med 1995; 52: 587–92.Google Scholar
  10. 10.
    Hueper WC, Wiley F, Wolfe HD. Experimental production of bladder tumors in dogs by administration of beta-naphthylamine. J Ind Hyg Toxicol 1938; 20: 46–84.Google Scholar
  11. 11.
    Case RAM, Hosker ME, McDonald DB, Pearson JT. Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part I. Br J Ind Med 1954; 11: 75–104.Google Scholar
  12. 12.
    International Agency for Research on Cancer. Overall Evaluations of Carcinogenicity: an Updating of IARC Monographs Volumes 1 to 42. Lyon, France: IARC 1987; IARC Monogr Eval Risks Humans, Supplement 7.Google Scholar
  13. 13.
    Mancuso TF, El-Attar AA. Cohort study of workers exposed to beta-naphthylamine and benzidine. J Occup Med 1967; 9: 277–85.Google Scholar
  14. 14.
    Goldwater LJ, Rosso AJ, Kleinfeld M. Bladder tumors in a coal tar dye plant. Arch Environ Health 1965; 11: 814–7.Google Scholar
  15. 15.
    Schulte PA, Ringen K, Hemstreet GP,et al. Risk assessment of a cohort exposed to aromatic amines. J Occup Med 1965; 27: 115–21.Google Scholar
  16. 16.
    Rubino GF, Scansetti G, Piolatto G, Pira E. The carcino-genic effect of aromatic amines: an epidemiologic study on the role of o-toluidine and 4,4'-methylene bis(2-methy-laniline) in inducing bladder cancer in man. Environ Res 1982; 27: 241–54.Google Scholar
  17. 17.
    Bulbulyan MA, Figgs LW, Zahm SH,et al. Cancer incidence and mortality among beta-naphthylamine and benzidine dye workers in Moscow. Int J Epidemiol 1995; 24: 266–75.Google Scholar
  18. 18.
    Zavon M.R, Hoegg U, Bingham E. Benzidine exposure as a cause of bladder tumours. Arch Environ Health 1973; 27: 1–7.Google Scholar
  19. 19.
    Tsuchiya K, Okubo T, Ishizu S. An epidemiological study of occupational bladder tumors in the dye industry in Japan. Am J Ind Med 1975; 32: 203–9.Google Scholar
  20. 20.
    Horton AW, Bingham EL. Risk of bladder tumors among benzidine workers and their serum properdin levels. JNCI 1977; 58: 1225–8.Google Scholar
  21. 21.
    Meigs JW, Marrett LD, Ulrich FU, Flannery JT. Bladder tumor incidence among workers exposed to benzidine: a thirty-year follow-up. JNCI 1986; 76: 1–8.Google Scholar
  22. 22.
    Bi WF, Hayes RB, Feng P,et al. Mortality and incidence of bladder cancer in benzidine-exposed workers in China. Am J Ind Med 1992; 21: 481–9.Google Scholar
  23. 23.
    Melamed MR. Diagnostic cytology of urinary tract carci-noma. A review of experience with spontaneous and carcinogen induced tumors in man. Eur J Cancer 1972; 8: 287–92.Google Scholar
  24. 24.
    Melick WF Bladder carcinoma and xenylamine. New Engl J Med 1972; 287: 1103.Google Scholar
  25. 25.
    Zack JA, Gaffey WR. A mortality study of workers employees at the Monsanto Company plant in Nitro, West Virginia. Environ Sci Res 1983; 26: 575–91.Google Scholar
  26. 26.
    Stasik MJ. Carcinomas of the urinary bladder in a 4-chloro-o-toluidine cohort. Int Arch Occup Environ Health 1988; 60: 21–4.Google Scholar
  27. 27.
    Ward E, Carpenter A, Markowitz S, Roberts D, Halperin W. Excess number of bladder cancers in workers exposed to ortho-toluidine and aniline. JNCI 1991; 83: 501–6.Google Scholar
  28. 28.
    Popp W, Schmieding W, Speck M, Vahrenholz C, Norpoth K. Incidence of bladder cancer in a cohort of workers exposed to 4-chloro-o-toluidine while synthesising chlor-dimeform. Br J Ind Med 1992; 49: 529–31.Google Scholar
  29. 29.
    Bonassi S, Merlo F, Pearce N, Puntoni R. Bladder cancer and occupational exposure to polycyclic aromatic hydro-carbons. Int J Cancer 1989; 44: 648–51.Google Scholar
  30. 30.
    Schumacher MC, Slattery ML, West DW. Occupation and bladder cancer in Utah. Am J Ind Med 1989; 16: 89–102.Google Scholar
  31. 31.
    Steineck G, Plato N, Alfredsson L, Norell SE. Industry-related urothelial carcinogens: application of a job-exposure matrix to census data. Am J Ind Med 1989; 16: 209–24.Google Scholar
  32. 32.
    Hours M, Dananche B, Fevotte J,et al. Bladder cancer and occupational exposure. Scand J Work Environ Health 1994; 20: 322–30.Google Scholar
  33. 33.
    Siemiatycki J, Dewar R, Nadon L, Gerin M. Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada. Am J Epidemiol 1994; 140: 1061–80.Google Scholar
  34. 34.
    Doll R, Vessey MP, Beasley RWR,et al. Mortality of gas-workers-final report of a prospective study. Br J Ind Med 1972; 29: 394–406.Google Scholar
  35. 35.
    Redmond CK, Ciocco A, Lloyd JW, Rush HW. Long-term mortality study of steelworkers. VI. Mortality from malignant neoplasms among coke oven workers. J Occup Med 1972; 14: 621–9.Google Scholar
  36. 36.
    Hammond EC, Selikoff IJ, Lawther PL, Seidman H. Inhalation of benzpyrene and cancer in man. Ann NY Acad Sci 1976; 271: 116–24.Google Scholar
  37. 37.
    Gustavsson P, Gustavsson A, Hogstedt C. Excess of cancer among Swedish chimney sweeps. Br J Ind Med 1988; 45: 777–81.Google Scholar
  38. 38.
    Steineck G, Norell SE, Feychting M. Diet, tobacco and urothelial cancer: a14-year follow-up of 16,477 subjects. Acta Oncol 1988; 27: 323–7.Google Scholar
  39. 39.
    Howe GR, Burch JD, Miller AB,et al. Tobacco use, occupation, coffee, various nutrients and bladder cancer. JNCI 1980; 64: 701–13.Google Scholar
  40. 40.
    McLaughlin JK, Blot WJ, Mandel JS, Schuman LM, Mehl ES, Fraumeni JF Jr. Etiology of cancer of the renal pelvis. JNCI 1983; 71: 287–91.Google Scholar
  41. 41.
    Silverman DT, Hoover RN, Albert S, Graff KM. Occupation and cancer of the lower urinary tract in Detroit. JNCI 1983; 70: 237–45.Google Scholar
  42. 42.
    Mommsen S, Aagard J. Occupational exposures as a risk indicator of male bladder carcinoma in a predominantly rural area. Acta Radiol Oncol 1984; 23: 147–52.Google Scholar
  43. 43.
    Schoenberg JB, Stemhagen A, Mogienicki AP, Altman R, Abe T, Mason TJ. Case-control study of bladder cancer in New Jersey. I. Occupational exposures in white males. JNCI 1984; 72: 973–81.Google Scholar
  44. 44.
    Thériault G, Tremblay C, Cordier S,et al. Bladder cancer in the aluminum industry. Lancet 1984; 1: 947–50.Google Scholar
  45. 45.
    Morrison AS, Ahlbom A, Verhoek WG, Aori IL, Ohno Y, Obata K. Occupation and bladder cancer in Boston USA, Manchester, UK and Nagoya, Japan. J Epidemiol Comm Health 1985; 39: 294–300.Google Scholar
  46. 46.
    Dunham LJ, Rabson AS, Stewart HL,et al. Rates, interview, and pathology study of cancer of the urinary bladder in New Orleans, Louisiana. JNCI 1968; 41: 683.Google Scholar
  47. 47.
    Tola S, Tenho M, Korkala ML, Jarvinen E. Cancer of the urinary bladder in Finland. Int Arch Occup Environ Health 1980; 46: 43–51.Google Scholar
  48. 48.
    Vineis P, Magnani C. Occupation and bladder cancer in males: a case-control study. Int J Cancer 1985; 35: 599–606.Google Scholar
  49. 49.
    Tremblay C, Armstrong B, Thériault G, Brodeur J. Estimation of risk of developing bladder cancer among workers exposed to coal tar pitch volatiles in the primary aluminum industry. Am J Ind Med 1995: 27: 335–48.Google Scholar
  50. 50.
    Steineck G, Plato N, Norell SE, Hogstedt C. Urothelial cancer and some industry-related chemicals: an evaluation of the epidemiologic literature. Am J Ind Med 1990; 17: 371–91.Google Scholar
  51. 51.
    International Agency for Research on Cancer. Occupational Exposures of Hairdressers and Barbers and Personal Use of Hair Colourants; Some Hair Dyes, Cosmetic Colorants, Industrial Dyestuff and Aromatic Amines. Lyon, France: IARC, 1993; IARC Monogr Eval Risks Humans, Vol. 57.Google Scholar
  52. 52.
    Huff J. Chemicals and cancer in humans: first evidence in experimental animals. Environ Health Perspect 1993; 100: 201–10.Google Scholar
  53. 53.
    Vineis P, Simonato L. Proportion of lung and bladder cancers in males resulting from occupation: A systematic approach. Arch Environ Health 1991; 46: 6–15.Google Scholar
  54. 54.
    Vainio H, Matos E, Boffetta P, Kogevinas M. Occupational cancer in developing and newly industrialized countries. Ann Acad Med Singapore 1993; 22: 170–81.Google Scholar
  55. 55.
    Kogevinas M, Boffetta P, Pearce N. Occupational exposure to carcinogens in developing countries. In: Pearce N, Matos E, Boffetta P, Kogevinas M., eds. Occupational Cancer in Developing Countries. Oxford, UK: Oxford University Press, 1994; IARC Sci. Pub. No. 129: 63–95.Google Scholar
  56. 56.
    Xue-Yun Y, Ji-Gang C, Yong-Ning H. Studies on the relation between bladder cancer and benzidine or its derived dyes in Shanghai. Br J Ind Med 1990; 47: 544–52.Google Scholar
  57. 57.
    Zheng W, Mc Laughlin J, Gao Y, Silverman DT, Gao R, Blot WJ. Bladder cancer and occupation in Shanghai, 1980–84. Am J Ind Med 1992; 21: 877-85.Google Scholar
  58. 58.
    Notani PN, Shah P, Jayat K, Balakrishnan V. Occupation and cancers of the lung and bladder: a case-control study in Bombay. Int J Epidemiol 1993; 22: 185–91.Google Scholar
  59. 59.
    International Agency for Research on Cancer. Tobacco Smoking. Lyon, France: IARC, 1986; IARC Monogr Eval Risks Humans, Vol. 38.Google Scholar
  60. 60.
    Vineis P. Epidemiological models of carcinogenesis: the example of bladder cancer. Cancer Epidemiol Biomark Prev 1992; 1: 149–53.Google Scholar
  61. 61.
    Bartsch H, Malaveille C, Friesen M, Kadlubar FF, Vineis P. Black (air cured) and blond (flue cured) tobacco-Cancer risk IV: Molecular dosimetry studies implicate aromatic amines as bladder carcinogens. Eur J Cancer 1993; 29A: 1199–207.Google Scholar
  62. 62.
    Talaska G, Al-Juburi AZSS, Kadlubar FF. Smoking-related carcinogen-DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc Natl Acad Sci USA 1991; 88: 5350–454.Google Scholar
  63. 63.
    Talaska G, Schamer M, Skipper P,et al. Detection of carcinogen-DNA adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin adducts, and urinary mutagenicity. Cancer Epidemiol Biomark Prev 1991; 1: 61–6.Google Scholar
  64. 64.
    Vineis P, Talaska G, Malaveille C,et al. DNA adducts in urothelial cells: relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke. Int J Cancer 1996; 65: 314–6.Google Scholar
  65. 65.
    Vineis P, Bartsch H, Caporaso N,et al. Genetically-based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens. Nature 1994; 369: 154–6.Google Scholar
  66. 66.
    D'Errico A, Taioli E, Chen X, Vineis P. Genetic metabolic polymorphisms and the risk of cancer: a review of the literature. Biomarkers 1996; 1: 149–73.Google Scholar
  67. 67.
    Sköv T, Sprogel P, Engholm, Frolund C. Cancer of the lung and urinary bladder in Denmark, 1943–87: a cohort analysis. Cancer Causes Control 1991; 2: 365-9.Google Scholar
  68. 68.
    Hartge P, Harvey EB, Linehan WM,et al. Unexplained excess risk of bladder cancer in men. JNCI 1990; 82: 1636–40.Google Scholar
  69. 69.
    Anton-Culver H, Lee-Feldstein A, Taylor TH. The association of bladder cancer risk with ethnicity, gender and smoking. Ann Epidemiol 1993; 3: 429–33.Google Scholar
  70. 70.
    Cantor KP, Lynch CF, Johnson D. Bladder cancer, parity and age at first birth. Cancer Causes Control 1992; 3: 57–62.Google Scholar
  71. 71.
    Fenech M, Neville S, Rinaldi J. Sex is an important variable affecting spontaneous micronucleus frequency in cytoki-nesis-blocked lymphocytes. Mutation Res 1994; 313: 203–7.Google Scholar

Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • Paolo Vineis
    • 1
  • Roberta Pirastu
    • 1
  1. 1.Dipartimento di Scienze Biomediche e Oncologia UmanaUnit of Cancer EpidemiologyTorinoItaly

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